We propose to develop a computer software simulation system for single photon and positron emission tomography, SimSET, which is designed to realistically model the behavior of imaging systems for complex distributions of attenuation media and isotopes. In addition, we will use SimSET to: 1) evaluate techniques for scatter correction in non-uniform attenuation media and 2) study the effects of imaging system characteristics and local tissue heterogeneity on the accuracy with which parameters of kinetic models of physiological processes can be estimated. The SimSet system includes an editor to define an object in terms of attenuation values. The object is divided into many small voxels and a Monte Carlo routine (incorporating options for including daughter gamma rays, branching ratios, and positron range) is then used to track photons from each voxel to build a master history file of photons. The system can also generate a file describing the energy deposited in each voxel of the object to allow the study of local dosimetry. An isotope distribution (static or time varying) is then defined by the user or generated by a kinetic model and is used to select an appropriate emitted photon list from the master file. In this manner, one master file can generate emitted photon lists for arbitrary isotope distributions. The emitted photon list is then processed by a detector system simulator that includes tracking photons through the collimator, detector interaction, position decoding simulation and count rate effects (pileup and accidentals). Finally, an image reconstruction and analysis module produces images from the detected events and provides measurements of image parameters and comparisons to the original isotope distribution. In addition to the unique method of producing the emitted photon lists from the master files (thus saving large amounts of computation time for complex objects), SimSET will also be unique in that it is designed to be transportable to other laboratories. Individual modules can be modified or extracted as needed. The photon history libraries and associated emitted list generator can be used to produce photon history lists for other software systems.